Human African Trypanosomiasis (HAT) is transmitted by the tsetse fly vector, T. brucei gambiense and rhodensiense, and if untreated, is lethal. Current treatments are poor. In particular, the side effects for the treatment of the second stage infection (CNS infection) are very serious. There is therefore an unmet need for the development of new approaches to the development of endoperoxide-containing compounds as lead compounds for HAT.